Anti-inflammatory Effects of a P-coumaric Acid and Kojic Acid Derivative in LPS-stimulated RAW264.7 Macrophage Cells

Numerous derivatives of natural substances have been synthesized to improve their functionality while avoiding the risk of side effects. Both kojic acid and p-coumaric acid are natural products with known anti-inflammatory properties. In this study, we synthesized an ester derivative of kojic acid and p-coumaric acid, 5-Hydroxy-4-oxo-4H-pyran-2-yl-methyl (E)-3-(3-hydroxyphenyl) acrylate (compound 3), and evaluated its synergistic anti-inflammatory effects. To determine the anti-inflammatory activity of compound 3 in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells, the degree of inhibition of nitric oxide (NO) production, a typical inflammatory mediator, was measured. Kojic acid and p-coumaric acid individually showed no inhibition at 100 μM, whereas compound 3 showed 60% inhibition at the same concentration. Furthermore, we investigated the change in activity of NF-κ B, a key transcription factor in inflammatory response, using RAW264.7 Gaussia luciferase reporter cells. Compound 3 suppressed the activation of NF-κB by approximately 32% at 25 μM. However, 200 μM of kojic acid and p-coumaric acid inhibited NF-κB activation by 20% and 15%, respectively. Taken together, our data suggest that the anti-inflammatory effect of compound 3 is due, at least in part, to the inhibition of NF-κB activation.